We propose a largely retrospective study of the relationship between sleep apnea severity and subcortical hyperintensities (SH) observed on brain MRI, the degree to which endothelial function mediates this relationship, and the degree to which SH predict functional decline longitudinally. We will apply quantitative image analysis techniques to the Sleep Heart Health Study/Cardiovascular Health Study (SHHS/CHS) data set to identify SH, a marker of rnicrovascular disease. We will also follow-up with participants to gather new data on quality of life, cognitive functioning, functional abilities, depression, and cerebrovascular events to determine the relationship between SH at one time point and change in these variables over time. The SHHS and CHS are overlapping, community-based studies of the relationship between sleep-disordered breathing and vascular disease. Sleep apnea is a serious health problem associated with an increased risk of hypertension, heart disease, and stroke. It is significantly more prevalent among older adults than among younger populations, and may contribute uniquely to vascular disease in older adults. Our preliminary data suggest a relationship between apnea severity and endothelial dysfunction, suggesting a direct effect on the integrity of the blood vessel. Compelling evidence exists indicating an association between apnea and large vessel stroke, and our pilot data also suggest that apnea is related to small vessel damage. SH have been identified as a predictor of stroke, functional impairment, and mortality in some populations. This study represents the first longitudinal investigation of the contribution of sleep apnea to SH in older adults and involves innovative techniques for the analysis of the existing SHHS/CHS data set. This application represents the collaborative effort of a team of researchers in the areas of sleep apnea and the quantitative measurement of SH. The findings from this study are expected to inform methods to prevent and/or treat vascular disease in the elderly. The specific aims of this study are to: (1) examine the relationship between sleep apnea and SH in the elderly, to (2) determine the degree to which endothelial function mediates this relationship, and (3) to determine the degree to which SH predict functional decline longitudinally. We expect to analyze data on approximately 1,120 participants based on our preliminary studies with this data set. [unreadable] [unreadable]